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Interferons are of two types
Type I (interferon α and β) and type II (interferon γ). Interferon α is produced by lymphocyte, β by fibroblast, and γ by T lymphocytes upon viral infection. The type of interferon are less or more potent against the class of virus species, for example, interferon α and β inhibits the vesicular stomatitis and encephalomyocarditis viruses better than interferon γ while interferon γ works better in case of vaccinia and reovirus infection.
How are interferons produced?
Generally all viruses can induce type-1 interferon production. Production of type-1 interferon is more pronounced in case of RNA viruses as compared to DNA viruses. In addition bacterial lipopolysaccharide and synthetic dsRNA analogs are known inducers of interferons. As a matter of fact dsRNA is a potent activator of interferon. dsRNA induce intereferon production by JAK/STAT signaling pathway. Toll-like-receptor 3 (TLR3) in presence of dsRNA can induce interferons by an alternate pathway. TLR7, TLR8, and TLR9 also induce interferon production through interferon regulatory factor 5 and 7 (IRF-5 and -7). Retinoic acid inducible gene 1 (RIG-1) activates interferon production by activating IRF- 3 and -7.
Interferons trigger signal transducer and activator of transcription (STAT) complexes by coordinating with their specific receptors. STATs belong to the family of transcription factors that control the expression of many immune system genes. Certain STATs are triggered by both type I and type II Interferons despite this each Interferon type can also activate unique STATs.
The classical Janus kinase – STAT (JAK-STAT) signaling pathway is the most explicit cell signaling pathway for all interferons which is also triggered by STAT activation.
The pathway involves coordination between JAKs and interferon receptors and phosphorylation of STAT1 and STAT2. Consequently this leads to the formation of a complex called as an Interferon-stimulated gene factor 3 (ISGF3). This complex comprises of STAT1, STAT2 and a third transcription factor called IRF9. After its formation the complex moves inside the cell nucleus where it binds to specific nucleotide sequences known as interferon stimulated response elements (ISREs) in the promoters of some specific genes called as interferon stimulated genes ISGs. Finally, coming together of ISGF3 and other transcriptional complexes triggered by interferon signaling initiates the transcription of genes responsible for secretion of interferons.